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The quantitative assessment of neuroblastoma cell content in bone marrow aspirates for response evaluation has been introduced recently. Data on the concordance of interobserver reports are lacking so far.

Objectives: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS. Methods: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes. Results: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study. Conclusions: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results. © 2018 Elsevier Inc.

Objective. To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet’s syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods. A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results. We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion. The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities. © 2018 Article author(s).

Uterine fibroids can have a significant economic impact on the National Healthcare Service and on Society overall (absenteeism and disability). Women with uterine fibroids have higher use of medical services and procedures. The management and treatment of uterine fibroids thence imposes a burden on the existing National Healthcare Service and it is important to understand the economic implications between treatment options and key cost drivers. Our analysis is limited to describe the disease management and pharmacological costs of uterine fibroids. Our focus is on clinical data, therapeutic options, treatment costs and unmet needs (therapeutic diagnostic path). Knowledge of these aspects can be a useful tool for the clinician in order to select the most effective treatment in clinical practice, tailored on patients' characteristics.

ASTRI SST-2M is an imaging atmospheric Cherenkov telescope developed by the Italian National Institute of Astrophysics (INAF) in the framework of the Cherenkov Telescope Array (CTA) project as an end-to-end prototype for the Small Size array. Large-, medium-, and small-sized telescopes will compose the CTA observatory that represents the next generation of imaging atmospheric Cherenkov telescopes and will explore the very high-energy domain from a few tens of GeV up to few hundreds of TeV. The ASTRI SST-2M telescope has been installed at the INAF-Catania observing station at Serra La Nave, on Mt. Etna (Sicily, Italy) in September 2014. In these 3 years of open-air operations the telescope has been commissioned and its opto-mechanical performance is now well understood. The apparatus was made ready to host its main scientific instrument, the camera with Silicon-Photomultiplier based detectors. This contribution is a status report on the complete ASTRI SST-2M telescope assembly including the electro-mechanical structure and the optical system.

Neopterin is specifically produced by interferon-activated macrophages, and it may be considered a marker of cellular immunity. In 40 newly diagnosed and 38 longer standing type 1 (insulin-dependent) diabetics the relationship between urinary neopterin levels and islet cell antibodies (ICA) was investigated. Raised urinary neopterin levels were found in 30 ICA positive (mean +/- SD: 729.8 +/- 602.1 mumol/mol creatinine, p = 0.0001) and 10 ICA negative (433.4 +/- 191.2 mumol/mol creatinine, p = 0.0005) diabetics at onset of disease compared with age-matched control subjects (118.1 +/- 33.2 mumol/mol creatinine). No significant difference in urinary neopterin levels was observed between diabetic groups. After the first stages of disease (greater than 5 months from onset), a significant difference (p = 0.0002) in urinary neopterin excretion was found between longer standing ICA positive patients and controls, but not between ICA negative diabetics and controls. In longer standing diabetics, neopterin levels were significantly higher in ICA positive patients than in ICA negative patients (544.6 +/- 341.3 versus 201.7 +/- 180 mumol/mol creatinine, p = 0.0002). No correlation between newly diagnosed or longer standing patients and HbA1c levels was found. Our results suggest that increased neopterin excretion in type 1 diabetes seems to be a sensitive indicator for the activation of cell-mediated immunity even when ICA are undetectable.

We have studied 27 insulin-dependent diabetic patients since diagnosis for a period of six months; at diabetes onset and later on, ICA were found in 17 of them, whereas they were undetectable in 10 patients: age was remarkably homogeneous in the two groups. At diabetes onset, no significant differences were found in insulin requirement between ICA positive and ICA negative patients; however, six months after diagnosis, we observed that insulin requirement to keep metabolic control was significantly higher in ICA positive than in ICA negative subjects (0.515 +/- 0.2 U/Kg versus 0.22 +/- 0.15 U/Kg, p less than 0.001). Only one remission has been detected in ICA positive group (insulin requirement less than 0.25 U/Kg), while four ICA negative patients had complete remission and three had partial remission. ICA positive patients showed fasting C-peptide values higher than ICA negative (0.5 +/- 0.28 ng/ml versus 1.4 +/- 0.5 ng/m.; p less than 0.001, at rest; 1.1 +/- 0.6 ng/ml; versus 2.6 +/- 1.0 ng/ml, 6 minutes after stimulus; p less than 0.05). Our study suggests that presence and persistence of ICA may be considered an early and predictive marker for a worse beta cell function restoration resulting in a higher insulin requirement.

Interleukin (IL)-6 is a multifunctional cytokine with a critical role in inflammatory, immunoregulatory and haemopoietic responses. Its receptor consists of an ubiquitously expressed membrane transducing element (gp130) and of the specific element IL-6R-alpha (gp80), present only on hepatocytes and some leukocyte subsets. IL-6R-alpha also exists as soluble protein (sIL-6R) that, in the presence of IL-6, forms a complex able to bind gp130 and, thanks to the mechanism called trans-signaling, transduces IL-6 effect through tyrosine phosphorylation and activation of the signal transducer and transcription activator (STAT)-3. The aim of this study was to analyze the bidirectional relationships between platelet aggregation and IL-6-dependent effects. While platelets do not produce IL-6, we found that resting platelets express gp130, but not gp80, on their membranes. Upon activation by thrombin or calcium ionophore A23187, but not by ADP, the IL-6R-alpha is released in soluble form, while cangrelor, the specific inhibitor of P2Y12 receptor, can partially inhibit sIL-6R release. This sIL-6R is biologically active and, in the presence of IL-6, can trigger IL-6 trans-signaling, inducing an autocrine activation loop (as measured by an increase in gp80 and gp130 content) and STAT3 phosphorylation. On the other hand, IL-6 trans-signaling has no effect on platelet degranulation or aggregation by itself, nor on thrombin-induced platelet aggregation. Our data add an important piece to the puzzle of thrombosis and inflammation: in the presence of IL-6, which can be produced by stressed endothelial cells, the platelet-derived IL-6 trans-signaling could be crucial for the evolution of inflammation within a damaged vessel.